Introduction. The aim of our study was to assess the efficacy of hypertonic dextrose infiltrations for pain control in individuals with rotator cuff tendinopathy and to assess the characteristics of the treatment and the presence of side effects or adverse reactions through a systematic review and meta-analysis. Methods. The search for the articles was performed in the electronic databases PUBMED, EMBASE, SCOPUS, SCIELO, DIALNET and Google Scholar, published up to August 2020. The keywords used were "prolotherapy" or “proliferation therapy” or "hypertonic dextrose infiltrations" or "hypertonic dextrose injection" and "Rotator Cuff" or "Rotator Cuff Injury" or “Rotator Cuff Tear” or “Rotator Cuff Tendinosis” or "supraspinatus". The effectiveness of hypertonic dextrose infiltrations was expressed as standardized mean difference (d) and 95% CI. Results. In the pooled analysis, hypertonic dextrose infiltrations were an effective intervention to reduce long-term pain in patients with rotator cuff tendinopathy when compared to controls; furthermore, in the individual analyses, hypertonic dextrose infiltrations were more effective in the short, medium and long terms than non-invasive treatments, and more effective in the long-term than infiltrations with local anesthetics. On the other hand, hypertonic dextrose infiltrations were not more effective than injections with corticosteroids or PRP. Finally, no complications or serious adverse effect were observed when hypertonic dextrose infiltrations were used. Conclusions. We found that hypertonic dextrose infiltrations reduced pain in individuals with rotator cuff in the long-term. Hypertonic dextrose infiltrations could be an alternative to non-invasive treatments when no favorable results can be achieve. However, due to the small number of studies included in this meta-analysis, new studies are necessary to clarify the efficacy and safety of this intervention.